Safety and effectiveness of all-oral and injectable-containing, bedaquiline-based long treatment regimen for pre-XDR tuberculosis in Vietnam

Abstract

Background: The World health organization (WHO) recently recommended standardized all-oral shorter regimens for rifampicin resistant Tuberculosis (RR-TB). For highly resistant Tuberculosis patients such as pre-XDR-TB: RR-TB plus additional resistance to fluoroquinolones (FQ), the 6–9-months bedaquiline (bedaquiline)-based regimens or BDQ-based long regimens are recommended. The role of second-line injectable (SLI) drugs in the treatment of drug resistant TB is restricted because of safety concerns. Nevertheless, it is not well-known how all-oral long regimens (BDQ-long) perform compared to SLI-containing long regimens (BDQ/SLI-long) in terms of safety and effectiveness among patients with highly resistant TB.Method: A prospective observational cohort of patients with RR-TB additionally resistant to fluoroquinolones and/or second-line injectable, treated with either BDQ-long or BDQ/SLI-long regimens according to the guidance of the National Tuberculosis Program of Vietnam, enrolled between December 2015 and June 2017.Results: Of 99 patients enrolled, 42 (42%) patients were treated with BDQ-long and 57 (57%) with BDQ/SLI-long. More than 85% of patients were previously exposed to both FQ and SLI. FQ and SLI resistance were confirmed in 28 (67%) and 41 (98%) in the BDQ-long cohort and 48 (84%) and 17 (30%) in the BDQ/SLI-long cohort, respectively. Treatment success was achieved among 29 (69%) and 46 (81%) patients on the BDQ-long and BDQ/SLI-long regimen, respectively (p = 0.2). For both regimens, median time to first smear/culture sputum conversion was 2 months. All patients experienced at least one adverse event (AE) and 85% of them had at least one severe Adverse events. The median time to a first severe adverse event was 2 months. Among patients treated with BDQ-long a higher proportion of patients had three QT-prolonging drugs in the regimen (26.2% versus 7.0%; p = 0.009). The severe prolonged QTcF was observed in 22 (52.4%) and 22 (38.6%) patients on BDQ-long and BDQ/SLI-long, respectively. Overall, 30 (30%) patients had to either temporary or permanently discontinued or more TB drugs due to AEs.Conclusion: Treatment success was similar for both all-oral and SLI-containing BDQ-based long regimens in highly resistant TB patients. Both regimens had a similar high frequency of AEs. For both BDQ-long and BDQ/SLI-long regimens active AEs monitoring is essential.

Efficacy and safety of bedaquiline containing regimens in patients of drug-resistant tuberculosis: An updated systematic review and meta-analysis

“…In total, 41 studies are included in the updated version of this review. The studies [10] , [11] , [12] , [13] , [14] , [15] , [16] , [17] , [18] , [19] , [20] , [40] , [41] , [42] , [43] , [44] , [45] , [46] , [47] , [48] , [49] , [50] , [51] , [52] , [53] , [54] , [55] , [56] , [57] , [58] , [59] , [60] , [61] , [62] , [63] , [64] , [65] , [66] , [67] , [68] , [69] were divided into two groups: 36 observational studies including a total of 9,934 patients, and 5 experimental studies including a total of 468 patients. The patient’s mean age was 36.2 years.…”

“…A meta -analysis was conducted in 2021 that pooled the results of these studies [21] . However, results from additional well-designed observational and experimental studies were published [19] , [20] , [40] , [41] , [42] , [43] , [44] , [45] , [46] , [47] , [48] , [49] , [50] , [51] , [52] , [53] , [54] , [55] , [56] , [57] , [58] , [59] , [60] , [61] , [62] , [63] , [64] , [65] , [66] , [67] , [68] , [69] . To better analyze the effectiveness and safety of bedaquiline in MDR-TB, we conducted an updated meta -analysis.…”

Study of Culture Conversion in Drug-Resistant Pulmonary Tuberculosis on All-Oral Longer Regimen at IGIMS, Patna

“…[ 15 16 17 ] However, some researchers reported the mean age group of patients of MDR-TB on the higher side in the fifth decade of life which might be probably due to variations in socio-demographic patterns between countries [ Table 2 ]. [ 18 ]…”

“…[ 22 ] Nguyen reported culture conversion to negative in 60% and 86.7% of patients at 2 and 6 months, respectively, while Kim J reported culture conversion to negative in 45.7% and 60% at 4 and 8 months, respectively. [ 18 20 ] Khan et al . [ 23 ] in their study reported 85.5% culture conversion at 6 months duration of treatment in MDR-TB patients.…”